Percutaneous biopsy

CHAPTER 22  Percutaneous biopsy Anne M. Covey and Lynn A. Brody

OVERVIEW Image-guided needle biopsy is the mainstay for diagnosis of nonpalpable masses almost anywhere in the body. The indications for biopsy continue to evolve, and although percutaneous biopsy of a given mass is possible, biopsy is not always indicated. As with any invasive procedure, percutaneous biopsy has associated risks that should be weighed before the procedure. Needle biopsy is warranted when the result of the biopsy will influence patient management. These indications include establishing a diagnosis before surgery or in patients who are not surgical candidates, evaluation of organ dysfunction, and obtaining material for receptor or gene mutation evaluation. While we enter the era of personalized medicine, this last indication is becoming increasingly important (see Chapter 9). Several methods are available to obtain tissue, including biopsy by percutaneous needle or by endoluminal and transvenous techniques. Needles ranging in size from 25 to 14 gauge are typically used, and outside the central nervous system, a biopsy can be obtained from almost any abnormality that can be imaged. Most needles contain an inner stylet, which is removed when the needle is appropriately positioned immediately before obtaining the specimen; the stylet prevents the needle from coring interposed structures and accumulating nontarget material before optimal placement. Smaller “fine” needles (25 to 20 gauge) are used to obtain cytologic specimens or to obtain samples for culture or flow cytometry. Larger needles (20 to 14 gauge) are used to obtain tissue cores when histologic material is required to assess tissue architecture. Common malignancies in which core specimens may be preferred for diagnosis include lymphoma, sarcoma, thymoma, and mesothelioma. Core biopsy is necessary for parenchymal organ biopsy in the setting of organ dysfunction/failure. Core material may also be required to diagnose well-differentiated hepatocellular carcinoma (HCC) or benign hepatic tumors. Tissue cores also may be preferred for immunohistochemical staining (IHC) and/or mutational analysis in patients for whom targeted therapies are being considered; most pathology laboratories have IHC validated for formalin-fixed material. In many laboratories however, fine needle biopsy specimens are sufficient for these purposes. Immunochemistry may be performed using a cell block prepared from a fine needle biopsy, provided there are an adequate number of cells, the appropriate solution is selected for the cells, and appropriate panels are selected (Fowler & Lachar, 2008); mutational analysis can also be performed from cytologic material (Boldrini et al, 2007). A number of different strategies and technologies are being developed and used to allow mutational analysis of very small amounts of DNA, further enhancing the utility of fine needle biopsy (Kanagal-Shamanna et al, 2014). Different operators and laboratories may also have individual preference based on

equipment and technique. Optimal results may be achieved when both fine needle and core biopsy are performed and material is considered jointly (Sigel et al, 2011; Stewart et al, 2002). To increase the likelihood of a diagnostic biopsy and to minimize complications, a high-quality imaging study should be available for review both when the biopsy is being planned and when it is performed. In some cases, careful review of imaging studies may provide a definitive diagnosis, obviating the need for biopsy. Review of preprocedure imaging also influences selection of the most appropriate modality for guidance and patient positioning during the procedure so that potential obstacles, such as interposed lung, bowel, or blood vessels, may be anticipated and, optimally, avoided. In addition, knowledge of imaging findings allows appropriate discussion of relevant risks when informed consent is obtained. With proper preprocedure imaging, the biopsy can be planned to avoid unusual or unsustainable positions, complex needle angulation, and challenging breathing instructions. Further, when performing biopsies under computed tomography (CT) guidance, careful planning may help reduce the radiation dose to the patient; in many cases, especially those performed using CT fluoroscopy, the majority of the patient dose is administered during the localizing/planning stage of the procedure (Sarti et al, 2012). With good-quality reference imaging, fewer localizing images may be required, and the localizing images may be acquired with lower dose parameters. Review of imaging studies before biopsy also facilitates targeting of the most viable area of a mass. While large masses outgrow their blood supply, they often become necrotic, and diagnostic material cannot be reliably obtained in a background of necrosis. Preprocedure contrast-enhanced CT, magnetic resonance imaging (MRI), and positron-emission tomography (PET) can allow optimal targeting of areas most likely to yield a diagnostic specimen.

BIOPSY TECHNIQUE Fine Needle Aspiration Limited scanning is performed to localize the lesion and select an approach; imaging is performed using one or more modalities that will, or may, be used to guide needle placement. The needle can either be advanced alone or coaxially, after placement of a guiding needle. The guiding needle is typically one gauge larger. The choice of “bare” needle placement versus use of a guiding needle is at the discretion of the operator. Advantages of a single-needle technique largely relate to ease of taking the specimen without having to work through another needle, as well as keeping the tract as small as possible. Advantages of a guiding needle include ease of taking multiple specimens from the same site and having access to embolize the track if so desired. 403

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Either alone, or through a guiding needle, a 25 to 20 gauge needle is advanced into the target lesion, and real-time (ultrasound [US], fluoroscopy, MR or CT fluoroscopy) or interrupted imaging (conventional CT or MRI) is performed to guide and assess needle position (Billich et al, 2008). Fine needles come in a variety of tip designs. Many physicians use a Chiba-style needle, in which the needle tip and inner stylet are beveled. Our preference is a Westcott-style needle: In addition to a beveled tip, it has a notch in the sidewall of the needle just proximal to the tip; this facilitates the operator’s ability to choose more precisely the location from which the cells will be aspirated. When needle position has been confirmed, the needle is attached to a disposable syringe. The plunger of the syringe is retracted to apply suction while the needle is moved back and forth within the lesion to obtain a sample. The needle is withdrawn after suction is released, and the specimen is deposited on a glass slide. Smears are made from the biopsy specimen, and these may be used for immediate analysis (e.g., Diff-Quik) or fixed in ethanol for immunohistochemical stains. The residual material within the syringe and needle is rinsed in a cellpreserving solution for preparation of a cell block. The solution used for the cell block should be selected based on the suspected diagnosis, the need for special studies, and preference of the cytopathologist. For cases in which non-Hodgkin’s lymphoma is suspected, a specimen for flow cytometry may be prepared by rinsing the needle and syringe in a nutrient-rich culture medium (e.g., Roswell Park Memorial Institute medium). When infection is suspected, material can be set aside for culture. In the ideal situation, an on-site cytopathologist or cytotechnologist can provide an immediate interpretation of the sample; this has been shown to increase the sensitivity of the biopsy, shorten the procedure time, and minimize the number of passes required to obtain a diagnostic specimen (Nasuti et al, 2002; Tsou et al, 2009).

Core Biopsy The technique for localizing a lesion is identical for fine needle and core biopsies. To obtain a good core sample, a target lesion should ideally be at least 1 cm in maximum dimension, although we have found that useful core biopsy material can be obtained from even smaller lesions. Because of the typically larger needle size (14 to 20 gauge) used to perform a core biopsy, care should be taken to minimize the possibility of traversing medium-sized arteries, which lack the muscular wall of larger arteries and have an increased tendency to bleed; traversing the colon can result in peritonitis or abscess. Core biopsy needles come in a variety of sizes and styles, including biopsy “guns” and cutting needles that obtain histologic samples manually as the needle is passed back and forth within the lesion. To confirm adequacy of the specimen, a touch preparation may be prepared on a glass slide for immediate evaluation by a cytopathologist or cytotechnologist. Before placement in formalin or saline, the core of tissue is placed on a glass slide and gently moved over the slide to allow some cells to collect on the surface. Care should be taken to avoid excessive vigorous touch preparations, because this has been shown to deplete the cellularity and DNA content of the specimen (Rekhtman et al, 2015). In addition to the tissue sample, material that is suitable for cytology is often collected at the same time, and this increases the diagnostic yield of the procedure. Core samples

are commonly placed in formalin. Occasionally, specimens may be sent “fresh” to pathology in saline or on saline-soaked gauze for special studies. Because cells placed in saline eventually undergo cell lysis related to osmotic shifts of saline into the cell, a specimen in saline needs to be fixed or frozen within a few hours to avoid deterioration of the tissue sample. Tissue also may be snap frozen for future studies. The preferred method for processing tissue may vary from institution to institution, and the preference of the pathologists reviewing the material should be determined before initiating a biopsy. For core biopsies obtained to evaluate organ parenchyma, compared with side-notch needles, end-cut needles may yield more diagnostic samples in terms of number of portal triads or glomeruli (Constantin et al, 2010). In the setting of organ dysfunction or failure, no touch preparation is required; specimens are sent in formalin or saline, depending on the indication and the preference of the pathologist. As mentioned earlier, many authors advocate performing both fine needle and core biopsy to maximize the diagnostic yield of every given biopsy (Sigel et al, 2011; Stewart et al, 2002). Core biopsy may be particularly useful to distinguish a well-differentiated HCC from nodular regeneration in the setting of cirrhosis (see Chapter 76) and in confirmation of benign diagnoses, including hemangioma, adenoma, and focal nodular hyperplasia (Kulesza et al, 2004; Kuo et al, 2004) (see Chapter 90A), although recent literature describes findings that may increase the diagnostic accuracy of fine needle biopsy for HCC versus cirrhotic nodules (Geramizadeh et al, 2012). Yang and colleagues (2004) described an interesting method of distinguishing well-differentiated HCC from benign hepatic lesions by using the physical features of the smear from the fine needle aspirates; namely, the smear in malignant lesions will appear finely granular, whereas a benign lesion would produce fragments of rigid fine needle cores. The authors attribute this to the reticulin status of the tissue.

IMAGING GUIDANCE Ultrasound Ultrasound (see Chapter 15) is commonly used to guide percutaneous biopsies of the liver because it is widely available, inexpensive, and portable. US may be used at the bedside or in patients in whom CT guidance is impractical. Lesions larger than 1 cm are often visible, and US allows real-time visualization of the needle while it courses from the skin into the lesion. This is especially helpful in small lesions that move with respiration and are difficult to target with interrupted imaging modalities. Visualization of smaller-caliber needles may be difficult, although many manufacturers make needles specially designed to enhance visibility with US. Another advantage of US guidance is the capability of multiplanar imaging and the absence of ionizing radiation—a benefit to both the patient and the operator. This is particularly useful in finding a route to lesions at the hepatic dome that avoids aerated lung and eliminates the risk of causing pneumothorax. Because CT provides a two-dimensional image, complex triangulation often is required to accomplish the same result. Doppler imaging is occasionally helpful in performing a biopsy by enhancing the localization of small lesions. US contrast agents may help identify the most viable regions of a tumor. Limitations of US include interoperator variability and poor transmission through air, fat, and bone, which limits the

Chapter 22  Percutaneous biopsy



visualization of some lesions. Additionally, patients who are sedated for biopsy may not be able to cooperate with breathing instructions necessary to facilitate visualization of some masses, including small lesions or those high in the hepatic dome.

Computed Tomography Computed tomography (see Chapter 18) is a common modality for guiding percutaneous biopsies because it provides superb anatomic detail, which gives the operator the ability to plan a path from skin to lesion using the safest approach, clearly visualizing interposed structures. CT is the imaging modality of choice for biopsies of the lung, pancreas, adrenal glands, abdominal and retroperitoneal lymph nodes, and bone and liver lesions that are not well visualized with US or when biopsy is performed by operators who are not skilled with US.

Computed Tomographic Fluoroscopy Many manufacturers now offer CT fluoroscopy as an option on diagnostic scanners. This produces CT images in near real time. It does expose the operator to ionizing radiation and requires that the operator wear lead, as with conventional fluoroscopy, but it is preferred by some physicians, owing to decreased time between needle manipulation and image availability.

Cone-Beam Computed Tomography Cone-beam computed tomography (CBCT), also sometimes referred to as C-arm CT, uses a flat-panel X-ray detector that rotates around the patient; the X-rays are divergent, forming a cone. Images can be reconstructed in multiple planes, and three-dimensional reconstruction can be performed and rotated in multiple planes. The soft tissue resolution is not comparable to conventional CT for abdominal and pelvic soft tissue, but the resolution for lung and bone is adequate for biopsy guidance. Further, available biopsy path–planning and needlenavigation software may assist the operator with needle placement (Floridi et al, 2014).

Magnetic Resonance Imaging Biopsies guided by MRI (see Chapter 19) have been made possible by the advent of open-bore MRI systems that provide access to patients during imaging and the availability of nonferrous biopsy needles and monitoring equipment. The superior contrast resolution of MR allows targeting lesions that are difficult to visualize with US and noncontrast CT, and the ability of MRI to image in any plane enhances the targeting of lesions that are not safe to approach or easy to access in the axial plane (Stattaus et al, 2008) (Fig. 22.1). Owing to high cost and limited availability, as well as a relative paucity of MRIcompatible biopsy needles, MR-guided biopsies are generally reserved for patients whose lesion cannot be seen or targeted with US or CT. In addition, it is necessary to ensure that nonferromagnetic, MRI-compatible equipment is on hand and that the patient is able to undergo MRI fluoroscopy. Fluoroscopy is useful for guiding bile duct biopsies. Benign and malignant biliary strictures (see Chapters 42 and 51) often have similar cholangiographic appearances and rarely can be distinguished based on imaging alone (Corvera et al, 2005; Hadjis et al, 1985). Lesions originating within the duct may be sampled by either an endoluminal (see Chapter 29) or a direct percutaneous approach (see Chapter 30). Percutaneous transhepatic biliary drainage allows direct access to the biliary tract

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for endoluminal biopsy, when satisfactory decompression of the biliary tree has been achieved. Biopsy forceps or brush-biopsy catheters can be used through the existing tract to obtain tissue samples of suspicious areas (Fig. 22.2). The sensitivity of forceps biopsy is in the range of 40% to 80%, higher than that of brush biopsy, which is in the range of 30% to 60%. Specificity for each approaches 98% (Govil et al, 2002; Stewart et al, 2001; Weber et al, 2008), and sensitivity is highest for intraductal lesions and when biopsy is done in conjunction with choledochoscopy to provide direct visualization of the lesion (Ponchon et al, 1996). Combining forceps and brush biopsy of the bile duct may provide superior results to either alone. Kulaksiz and colleagues (2011), noted sensitivity of brushing alone of 49%, forceps alone of 69%, and combined of 80%; specificity for malignancy was 100%. However, a recent report of a new percutaneous forceps biopsy technique cites sensitivity of 93.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 70%; overall accuracy was 94.2% (Patel et al, 2015). Alternatively, after the biliary tree is opacified, a direct percutaneous needle biopsy of a bile duct lesion may be targeted with fluoroscopy using a transhepatic approach (Chawla et al, 1989) (see Chapter 30). This technique is most useful for intrinsic bile duct lesions but may also be used to diagnose lesions adjacent to the bile duct. With this technique, contrast is injected into an indwelling biliary drainage catheter to delineate the targeted bile duct abnormality. A needle is advanced through the anterior abdomen to the lesion, and a specimen is obtained. Confirmation of accurate needle position is made by obtaining oblique fluoroscopic images and by real-time fluoroscopy, when the needle is seen to move the duct or the indwelling catheter or both (Fig. 22.3). Fluoroscopy may also be useful to guide percutaneous biopsy of lung nodules and for nontargeted transvenous biopsies of the liver or kidney.

Positron-Emission Tomography Occasionally, a lesion is only well demonstrated by 18Ffluorodeoxyglucose (FDG) PET imaging. In these cases, it is possible to use PET and CT to guide accurate needle placement. Certain lesions may also have varying FDG avidity; PET guidance allows the most hypermetabolic portion of a lesion to be targeted. Operators should be mindful of the patient as a source of radiation; the major source of radiation to the operator during PET-guided interventions was found to be the time spent in close proximity to the patient (Ryan et al, 2013) (see Chapter 17).

Other Guidance New technology is under development that allows fusion of multiple modalities. For example, CT and MRI scans can be overlaid with real-time US images to achieve the clarity of the one imaging modality and the real-time visualization capabilities of the other. PET images (see Chapter 17) also can be fused to demonstrate sites of highest metabolic activity. Additionally, robotic guidance systems have been piloted in an effort to optimize speed and accuracy of needle placement.

BIOPSY OF SPECIFIC SITES Liver Biopsy Percutaneous liver biopsy is performed to determine the nature of focal liver masses, the cause and extent of cirrhosis, or the

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FIGURE 22.1.  Magnetic resonance (MR)-guided percutaneous liver biopsy. A, Axial T1 MR after contrast administration shows a focal lesion in segment IV in a patient with hepatitis B. B, Noncontrast computed tomography in the same patient at the same level failed to show the lesion. C, The lesion was hypermetabolic on fluorodeoxyglucose positron-emission tomography. D, biopsy was successfully performed using MR guidance in the sagittal plane to avoid the risk of pneumothorax. The biopsy specimen confirmed the diagnosis of hepatocellular carcinoma.

cause of liver dysfunction (see Chapters 76 and 89). Modern cross-sectional imaging techniques, including US, CT, and MRI, allow percutaneous biopsy of both small and deep lesions to be performed on an outpatient basis with minimal morbidity. With current techniques, almost any liver lesion can be targeted percutaneously; many liver lesions larger than 5 mm are suitable for biopsy (Yu et al, 2001). Fine needle biopsy of liver lesions has a sensitivity of 69% to 97% (Ohlsson et al, 2002).

Focal Liver Lesions Focal liver lesions may be solitary or multiple. For a solitary lesion, several benign conditions—cyst, hemangioma, focal nodular hyperplasia, and adenoma—often can be diagnosed confidently by high-quality cross-sectional imaging, obviating the need for biopsy (Gibbs et al, 2004; Hussain et al, 2004; Kim et al, 2004) (see Chapters 15, 18, and 19). These

diagnoses should be considered in all solitary liver lesions, unless they are known to be new in the setting of a known cancer or in patients at risk for primary HCC. HCC may also be diagnosed based on imaging and clinical criteria (see Chapter 91). According to the American Association for the Study of Liver Diseases (AASLD) guidelines, in patients with cirrhosis, liver lesions identified on screening US that are larger than 1 cm may be diagnosed as HCC based on a single CT or MR imaging study demonstrating classic findings of arterial enhancement and portal venous or delayedphase washout (Bruix & Sherman, 2011); the National Comprehensive Cancer Network guidelines are the same for lesions 2 cm and larger, but for lesions 1 to 2 cm in size, they advise that two concordant imaging studies are necessary to confirm a diagnosis of HCC (Benson et al, 2009). When the diagnosis of HCC is considered, and these criteria are not met,

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Child B or C cirrhotic patients with tumor-nodes-metastasis classification stage I to III tumors greater than 3 cm and α-fetoprotein greater than 200 ng/mL. They also note, however, that accurate diagnosis of HCC is extremely important because confirmation of diagnosis alters the priority for liver transplantation (Rockey et al, 2009). Multifocal solid liver lesions most commonly represent metastatic disease. In such cases, biopsy may be requested to (1) confirm the presence of metastatic disease in a patient with a known primary, (2) establish tumor type and stage simultaneously at initial presentation, (3) acquire tissue for genetic analysis, and (4) obtain required samples for patients undergoing experimental therapies.

Liver Parenchyma Biopsy

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Core liver biopsy is used to grade and stage liver disease in patients with abnormal liver function studies, chronic hepatitis, and known or suspected cirrhosis (see Chapters 9D and 76). Gastroenterologists have historically performed most liver biopsies without imaging guidance; however, unusual anatomy, obesity, and other exigencies occasionally make imaging-guided biopsy advisable. Adequate tissue cores can be obtained with needles 20 gauge and larger, although needles 18 gauge and larger provide a more generous specimen for analysis (Guido & Ruggae, 2004; Maharaj et al, 1986). Schiano and colleagues (2005) further suggest that specimens of at least 1 cm in length are preferred. Biopsy may also be performed in transplanted livers and in living donors before transplant. Indications for this last group are controversial. Herrero and colleagues (2014) recommend following the recommendations of the Vancouver Forum (Barr et al, 2006) in performing biopsy in potential donors who have a clinical or imaging-based reason to do so, but not as a matter of routine.

Transvenous Biopsy

B FIGURE 22.2.  Biliary brush biopsy. A, Transhepatic cholangiogram shows a high bile duct stricture (arrow) Prior brush biopsy was nondiagnostic. B, A brush (curved arrow) was advanced to the stricture and used to obtain a specimen for cytology. The specimen was diagnostic of cholangiocarcinoma.

biopsy may be required. Smaller, encapsulated tumors are more likely to be well differentiated, and tissue cores may be required to distinguish a well-differentiated tumor from normal or cirrhotic liver. Because of the risk of tumor seeding (Chaudhry et al, 2004; Durand et al, 2007; Perkins, 2007), when a curative treatment is possible, biopsy for HCC should be performed only after consultation with a hepatobiliary surgeon and after referencing the most current imaging and clinical criteria. The AASLD position paper on liver biopsy reinforces caution based on concern for needle-track seeding, sampling error, and, based on a paper by Saborido and colleagues (2005), possible increased rate of recurrence posttransplant, although only in

Transjugular liver biopsy is a useful alternative to percutaneous biopsy in patients with coagulopathy or when hepatic venous pressure measurements are required (Behrens & Ferral, 2012; Garcia-Compean & Cortes, 2004). Although transvenous biopsy is seemingly more invasive than percutaneous biopsy, the risk of significant bleeding in patients with coagulopathy is minimized using a transvenous approach, because bleeding from the biopsy site tracks back into the venous circulation and not into the abdominal cavity as can happen with percutaneous biopsies. Proper technique to avoid puncture of the liver capsule is crucial to optimize safety. In this technique, a venous sheath is introduced into a hepatic vein, most commonly the right hepatic vein, typically from a right internal jugular approach. Pressure measurements may be obtained to evaluate the source (presinusoidal, sinusoidal, or postsinusoidal) and degree of portal hypertension. A biopsy needle is introduced through the sheath into the liver parenchyma to obtain histologic samples (Fig. 22.4). Care must be taken to avoid performing the biopsy in too peripheral an area of liver, because this increases the risk that the liver capsule will be punctured and that peritoneal hemorrhage will result. Transvenous biopsy is only used for nontargeted parenchymal biopsy; it cannot be used for biopsy of a focal lesion. Transvenous biopsy of the kidney also has been reported and may be useful for evaluation of renal dysfunction in coagulopathic patients (Misra et al, 2008). This may be particularly

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C FIGURE 22.3.  Percutaneous bile duct biopsy. A, Transhepatic cholangiogram shows a high bile duct stricture (marked by the clamp) of uncertain etiology. B, Under fluoroscopic guidance, a 22 gauge needle was used to target the stricture. C, Oblique imaging confirmed the position of the needle at the site of the bile duct stricture.

convenient in coagulopathic patients who require both parenchymal hepatic and renal biopsies.

Biopsy of Other Organs Adrenal Biopsy The adrenal gland is a common site of metastatic disease. This gland also is the site of many benign neoplasms, and

adenomas occur in 5% of individuals (Abecassis et al, 1985; Libe et al, 2002). Adrenal biopsy can often be avoided, because MRI or adrenal protocol CT can sometimes distinguish between an adenoma and a metastasis (Davarpanah & Israel, 2014; National Institutes of Health, 2002). In some cases, the mass remains indeterminate, and biopsy is indicated. Because of the posterior approach used for all left and

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some right adrenal biopsies, it is common to traverse the lung, introducing the possibility of a pneumothorax. The right adrenal gland can alternatively be targeted from a lateral, transhepatic approach to eliminate the risk of pneumothorax (Fig. 22.5). Some authors advocate placing patients in the ipsilateral decubitus position for adrenal biopsy, to take advantage of diminished aeration of the lower lobe of the lung in this position and decrease the likelihood of either putting the needle through lung, or using an out-of-plane trajectory to avoid lung (Odisio et al, 2012) (see Fig. 22.5C).

Pancreas Biopsy Despite the best efforts of clinicians and advances in imaging, most patients with pancreatic cancer still initially present with unresectable disease (see Chapter 59). Needle biopsy may be requested for tissue diagnosis so that treatment can be initiated, and it is essential to evaluate the preprocedure imaging carefully to determine the safest approach. Increasingly, endoscopic ultrasound (EUS) has become an excellent alternative to percutaneous biopsy (see Chapter 16). In cases where in which EUS-guided biopsy is not feasible or adequate material is not obtained, percutaneous biopsy may still be necessary. An anterior approach to the pancreas may be difficult because of interposed colon, spleen, or mesenteric vessels, which we would prefer not to traverse. We often prefer a posterior, transcaval approach (Sofocleous et al, 2004) or a transhepatic approach, particularly for lesions in the head or uncinate process (Fig. 22.6).

Retroperitoneal and Pelvic Biopsy A

B FIGURE 22.4.  Transjugular liver biopsy. A, Right hepatic venogram through a sheath placed via the right internal jugular vein. B, A 19-gauge automated flexible biopsy needle with a 20-mm throw (arrow) is advanced through a metal cannula and directed anteriorly as the biopsy specimen is obtained.

Most retroperitoneal and pelvic biopsies are performed to determine the cause of lymphadenopathy. When the patient has a known malignancy with the proclivity to spread via retroperitoneal lymphatics, needle biopsy is indicated, and this is generally easily and simply performed. When lymphoma is a consideration, biopsy specimens should be obtained either for flow cytometry and/or surgical pathology (cores), depending on local practice and expertise. Occasionally, a biopsy is performed to diagnose a soft tissue mass suspected to be a sarcoma. In patients who are candidates for resection, the approach to the lesion should be discussed with the surgeon, as they may wish to resect the needle path to minimize the risk of local recurrence. For primary diagnosis of sarcoma, histologic material is useful for classifying the sarcoma, and core biopsy should be performed. If recurrence is the issue, the diagnosis usually can be established on the basis of cytology alone. In women with pelvic masses that might be adnexal, needle biopsy should be performed only after the diagnosis of ovarian cancer has been excluded or after an oncologic gynecologist has been consulted. The biopsy procedure itself may result in peritoneal contamination, relegating the patient to intraperitoneal chemotherapy, when a simpler treatment regimen might have been possible. In addition to previously described guidance modalities, deep pelvic pathology is sometimes best approached using transrectal or transvaginal US guidance.

Lung and Mediastinum Biopsy Lung biopsies can be performed with CT, CT fluoroscopy, CBCT, or conventional fluoroscopy. The size, location, and nature of the target lesion, as well as operator experience, and available equipment determine which modality is used.

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FIGURE 22.5.  Adrenal biopsy. A, Transhepatic right adrenal mass (arrows) biopsy eliminates the risk of pneumothorax. B, Coronal reformat of a contrast enhanced computed tomography shows a right adrenal mass (arrows). C, With the patient positioned prone, there is interposition of lung between the skin and adrenal mass (arrows). D, With the patient in a right-side-down position, there is no need to traverse aerated lung for biopsy of the adrenal mass (arrows).

Mediastinal biopsies are usually performed using CT guidance. The size of the needle used and type of specimen acquired vary depending on the clinical indication. Diagnostic rates for needle biopsy of malignant lung lesions have been reported as greater than 90% (Swischuk et al, 1998). Lung biopsy may be useful to provide material in the setting of metastatic disease, primary malignancy, and/or infection. Personalized medicine is already making its mark in primary lung cancer. Not long ago, all cases of non–small-cell lung cancers were treated in a similar fashion. However, recent studies have shown that histologic subtype and certain molecular alterations influence the response to various chemotherapies and targeted agents (Moreira et al, 2012; Travis et al, 2010). For example, bevacizumab, a humanized monoclonal antibody targeted at endothelial growth factor, is contraindicated in patients with squamous cell lung carcinoma due to increased risk of pulmonary hemorrhage (Johnson et al, 2004). Patients with adenocarcinoma also respond better to the antifolate agent pemetrexed than those with squamous carcinoma (Scagliotti et al, 2008), and patients with adenocarcinoma and an epidermal growth factor receptor gene (EGFR) mutation have been shown to have a better response to

a tyrosine kinase inhibitor compared with chemotherapy in nonsmokers or former light smokers (Mok et al, 2009). Patients with adenocarcinoma and an EGFR mutation were also shown to do better when a tyrosine kinase inhibitor was used as maintenance after first-line treatment rather than as second-line therapy (Wang et al, 2011). The KRAS and ALK mutations have also been shown to influence response to treatment (Eberhard et al, 2005; Kwak et al, 2010).

Bone Biopsy Bone biopsies are often done using CT guidance. MRI and fluoroscopy may also be used. More recently, operators have described excellent results using CBCT with needle-guiding software (Tselikas et al, 2015). Bone biopsies are typically performed using larger needles (11 to 15 gauge) than those used for organ or soft tissue. Purely lytic lesions are the exception, because small-caliber needles will often suffice to document metastases and are able to penetrate bone in the setting of cortical destruction. For surgical candidates, the biopsy path should be discussed with the surgeon to ensure that violating an uninvolved compartment does not compromise a planned

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B FIGURE 22.6.  Transcaval pancreatic biopsy. A, Contrast-enhanced computed tomography scan shows a cystic mass (arrow) in the head of the pancreas in a patient with a history of non–small-cell lung cancer. B, Transcaval biopsy performed in the prone position with a 22 gauge needle confirmed the diagnosis of metastasis. The inferior vena cava is indicated by the arrows.

procedure. Liu and colleagues (2007) published useful anatomic guidelines for biopsy of bone tumors and further stress the need to consult with the surgeon to maximize each patient’s chance of getting optimal surgical treatment.

COMPLICATIONS OF PERCUTANEOUS BIOPSY Any invasive procedure has risks. Risks of biopsy include bleeding, pneumothorax, infection, bile leak, and needle-tract seeding of tumor. The risks vary depending on the organs involved. To minimize the risk of bleeding, we advocate that all patients should have appropriate laboratory work before biopsy, including a complete blood count and coagulation profile. Although criteria differ from institution to institution and from physician to physician, a platelet count of greater than 50,000 µL and an international normalized ratio (INR) less than 1.5 are acceptable in most cases. Biopsy in thrombocytopenic patients can be performed with platelet coverage, although the decision to proceed with biopsy should be considered

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carefully. For patients with an elevated INR, transfusion of plasma or supplementation with vitamin K is required. Elevated partial thromboplastin time (PTT) in patients not on heparin usually is due to circulating antiphospholipid cardiolipins and is not typically clinically significant. A test of bleeding time may be performed to evaluate the significance of an elevated PTT in select patients. It is advisable to have patients stop antiplatelet medications, if possible, to minimize the risk of bleeding; however, the risk of stopping antiplatelet therapy must be weighed against the risk of bleeding from the biopsy; occasionally, the balance favors performing the biopsy while the patient remains on his or her regular medication(s). The risk of significant bleeding after liver biopsy is less than 1% (Piccinino et al, 1986). In many cases, the bleeding is selflimited, and conservative management comprising observation and hydration will suffice. In patients with more significant bleeding and/or symptomatic hemorrhage, hepatic angiography and potential embolization of an injured artery may be required (Fig. 22.7). Some authors advocate placing absorbable gelatin sponge (Gelfoam) pledgets in the biopsy tract through the needle after core biopsy, but this has not been shown definitively to decrease the risk of major bleeding (Hatfield, 2008). Pain out of proportion to imaging findings after liver biopsy may be due to bile peritonitis (Ruben & Chopra, 1987). Care should be taken to minimize needle passes through the gallbladder, cystic duct, or dilated bile ducts. If the gallbladder is inadvertently punctured, it should be aspirated as completely as possible before removing the needle. Bile leaks resulting in discernible collections are rare after liver biopsy in the absence of downstream biliary obstruction. Adrenal masses and lesions in the dome of the liver sometimes require an approach for biopsy that crosses the lung base, putting patients at risk for pneumothorax. The two most common complications after lung biopsy include hemoptysis and pneumothorax (Covey et al, 2004). Hemoptysis occurs in approximately 10% of patients who undergo lung biopsy and is usually self-limited, but it can be frightening to the patient. Pneumothorax occurs in 20% to greater than 40% of patients after biopsy and requires placement of a chest tube in approximately 6% to 12% of cases. The risk of pneumothorax is typically related more to patient than technical factors, although depth of the target lesion, number of pleural surfaces transgressed, and patient positioning (prone positioning decreases the risk of pneumothorax) have been shown to affect the likelihood. Elderly patients and patients with underlying chronic obstructive pulmonary disease are more prone to pneumothorax requiring treatment (Covey et al, 2004; Hiraki et al, 2010; Takeshita et al, 2015). A symptomatic or enlarging pneumothorax is treated with a small-bore chest tube (generally 8 to 12 Fr) and often necessitates hospital admission. A number of methods have been described in an attempt to decrease the incidence of pneumothorax requiring chest tube placement after percutaneous lung biopsy. These include autologous blood patch injection into the needle track (Herman & Weisbrod, 1990), embolization of the needle track using gelatin sponge slurry (Tran et al, 2014), rapidly placing a patient in a “puncture-side-down” position following removal of the biopsy guiding needle (Kim et al, 2015), and use of commercial track plugs, among others. Although some studies showed a lower rate of pneumothorax requiring chest tubes in the “intervention group,” others did not; there is no consensus regarding

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PART 2  DIAGNOSTIC TECHNIQUES

A

which, if any, technique may be most useful in decreasing the rate of pneumothorax related to percutaneous lung biopsy. Hemorrhagic pericardial tamponade is a rare, potentially lifethreatening complication after mediastinal biopsy (Kucharczyk et al, 1982). Although hypoxemia may be a feature, this complication can be distinguished from iatrogenic pneumothorax clinically by the development of hypotension with narrowing of the pulse pressure and diminished amplitude of the electrocardiogram complex on the monitor. The diagnosis can be confirmed immediately by scanning the heart and pericardium, and it can be treated by directly placing a drainage catheter into the pericardial space. Needle-tract seeding after percutaneous biopsy is a worrisome complication. The interval between biopsy and appearance of a tract metastasis is 6 to 24 months (Kosugi et al, 2004; Schotman et al, 1999). The risk overall is likely greater than reported, but current understanding is that the risk in HCC is in the range of 2% to 3% (Perkins, 2007; Stigliano et al, 2007). Although the incidence is relatively small, the possibility of rendering a patient ultimately incurable because of tract or peritoneal seeding should be considered in the risk/benefit analysis for each patient. For this reason, some surgeons do not advocate percutaneous biopsy for patients with potentially resectable lesions highly suspicious for malignancy (Al-Leswas et al, 2008; Cha et al, 2002); this sentiment is particularly strong among transplant surgeons in regard to patients with HCC or other malignant disease undergoing evaluation for a new liver graft (see Chapter 115).

CONCLUSION B

C FIGURE 22.7.  Hemorrhage complicating liver biopsy. A, Contrastenhanced computed tomographic scan 5 days after liver biopsy shows a large subcapsular hematoma (curved arrow) with active extravasation of contrast from the liver mass (curved arrow). B, Angiography shows active extravasation (curved arrow) from peripheral segment VIII artery that was successfully embolized with stainless steel coils (C).

Percutaneous needle biopsy is a well-established and safe diagnostic tool, and it is an important instrument in the diagnosis of tumors, for determining the cause of organ dysfunction staging, and for documenting recurrent or metastatic disease. Increasingly, needle biopsy is essential to provide material for genetic analysis. Complications occur infrequently, and most are easily treated or self-limiting. Tract seeding has been reported but occurs infrequently. There is no such thing as a “negative” biopsy (Phillips et al, 1998). If a diagnosis of malignancy is not made, a specific benign diagnosis needs to be confirmed. If nonspecific findings are evident on cytology, including inflammatory or reactive changes, fibrous tissue, or normal site tissue, or, if atypical cells are present, another biopsy should be performed, or the lesion should be closely followed up, depending on the pretest probability of disease. The role of biopsy in patient management is evolving in tandem with the development of associated fields, including functional and molecular imaging. Until biopsies are no longer necessary, every effort should be made to keep morbidity low and diagnostic rates high. References are available at expertconsult.com.



REFERENCES Abecassis M, et al: Serendipitous adrenal masses: prevalence, significance and management, Am J Surg 149:783–788, 1985. Al-Leswas D, et al: Biopsy of solid liver tumors: adverse consequences, Hepatobiliary Pancreat Dis Int 7(3):325–327, 2008. Barr ML, et al: A report of the Vancouver Forum on the Care of the Live Organ Donor: lung, liver, pancreas, and intestine data and medical guidelines, Transplantation 81(10):1373–1385, 2006. Behrens G, Ferral H: Transjugular liver biopsy, Semin Intervent Radiol 29(2):111–117, 2012. Benson AB, et al: NCCN clinical practice guidelines in oncology: hepatobiliary cancers, J Natl Compr Canc Netw 7(4):350–391, 2009. Billich C, et al: CT-guided lung biopsy: incidence of pneumothorax after instillation of NaCl into the biopsy track, Eur Radiol 18(6):1146– 1152, 2008. Boldrini L, et al: Mutational analysis in cytolological specimens of advanced lung adenocarcinoma: a sensitive method for molecular diagnosis, J Thorac Oncol 2(12):1086–1090, 2007. Bruix J, Sherman M: Management of hepatocellular carcinoma: an update, Hepatology 53(3):1020–1022, 2011. Cha C, et al: Surgery and ablative therapy for hepatocellular carcinoma, J Clin Gastroenterol 35(Suppl 2):S130–S137, 2002. Chaudhry SI, et al: Preoperative biopsy of hepatocellular carcinoma renders 1 in 5 operable cases incurable [abstract], Br J Surg 91(Suppl 1):103, 2004. Chawla S, et al: Cholangiographically guided aspiration cytology in the management of malignant biliary obstruction, Indian J Gastroenterol 8:95–96, 1989. Constantin A, et al: Percutaneous US guided renal biopsy: a retrospective study comparing and 16 gauge end-cut and 14 gauge side notch needles, J Vasc Interv Radiol 21(3):357–361, 2010. Corvera CU, et al: Clinical and pathologic features of proximal biliary strictures masquerading as hilar cholangiocarcinoma, J Am Coll Surg 201:862–869, 2005. Covey AM, et al: Factors associated with pneumothorax following percutaneous lung biopsy in 443 consecutive patients, J Vasc Interv Radiol 15:479–483, 2004. Davarpanah AH, Israel GM: MR imaging of the kidneys and adrenal glands, Radiol Clin North Am 52(4):779–798, 2014. Durand F, et al: Liver transplantation for hepatocellular carcinoma: role of biopsy, Liver Transpl 13:S17–S23, 2007. Eberhard DA, et al: Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib, J Clin Oncol 23(25):5900–5909, 2005. Floridi C, et al: C-arm cone-beam computed tomography needle path overlay for percutaneous biopsy of pulmonary nodules, Radiol Med 199:820–827, 2014. Fowler LJ, Lachar WA: Application of immunohistochemistry to cytology, Arch Pathol Lab Med 132:373–383, 2008. Garcia-Compean D, Cortes C: Transjugular liver biopsy: an update, Ann Hepatol 3:100–103, 2004. Geramizadeh B, et al: Cytologic comparison between malignant and regenerative nodules in the background of cirrhosis, Hepat Mon 12(7):448–452, 2012. Gibbs JF, et al: Contemporary management of benign liver tumors, Surg Clin North Am 84:463–480, 2004. Govil H, et al: Brush cytology of the biliary tract: retrospective study of 278 cases with histopathologic correlation, Diagn Cytopathol 26: 273–277, 2002. Guido M, Ruggae M: Liver biopsy sampling in chronic viral hepatitis, Semin Liver Dis 24:89–97, 2004. Hadjis NS, et al: Malignant masquerade at the hilum of the liver, Br J Surg 72:659–661, 1985. Hatfield MK: Percutaneous imaging-guided solid organ core needle biopsy: coaxial versus noncoaxial method, AJR Am J Roentgenol 190(2):413–417, 2008. Herman SJ, Weisbrod GL: Usefulness of the blood patch technique after transthoracic needle aspiration biopsy, Radiology 176(2):395– 397, 1990. Herrero JI, et al: Is liver biopsy necessary in the evaluation of a living donor for liver transplantation?, Transplant Proc 46(9):3082–3083, 2014.

Chapter 22  Percutaneous biopsy 412.e1 Hiraki T, et al: Incidence and risk factors for pneumothorax and chest tube placement after CT fluoroscopy-guided percutaneous lung biopsy: retrospective analysis of the procedures conducted over a 9-year period, AJR Am J Roentgenol 194(3):809–814, 2010. Hussain SM, et al: Focal nodular hyperplasia: findings at state-of-theart MR imaging, US, CT and pathologic analysis, Radiographics 24:3–17, 2004. Johnson DH, et al: Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer, J Clin Oncol 22(11):2184–2191, 2004. Kanagal-Shamanna R, et al: Mod Pathol 27(2):314–327, 2014. Kim J, et al: An algorithm for the accurate identification of benign liver lesions, Am J Surg 187:274–279, 2004. Kim JI, et al: Rapid needle-out patient-rollover approach after cone beam CT-guided lung biopsy: effect on pneumothorax rate in 1,191 consecutive patients, Eur Radiol 25(7):1845–1853, 2015. Kosugi C, et al: Needle-tract implantation of hepatocellular carcinoma and pancreatic carcinoma after ultrasound-guided percutaneous puncture: clinical and pathologic characteristics and the treatment of needle-tract implantation, World J Surg 28:29–32, 2004. Kucharczyk W, et al: Cardiac tamponade as a complication of thinneedle aspiration lung biopsy, Chest 82:120–121, 1982. Kulaksiz H, et al: A novel method of forceps biopsy improves the diagnosis of proximal biliary malignancies, Dig Dis Sci 56:596–601, 2011. Kulesza P, et al: Cytopathologic grading of hepatocellular carcinoma on fine-needle aspiration, Cancer 102:247–258, 2004. Kuo FY, et al: Fine needle aspiration cytodiagnosis of liver tumors, Acta Cytol 48:142–148, 2004. Kwak EL, et al: Anaplastic lymphoma kinase inhibition in non-smallcell lung cancer, N Engl J Med 363(18):1693–1703, 2010. Libe R, et al: Long-term follow up study of patients with adrenal incidentalomas, Eur J Endocrinol 147:489–494, 2002. Liu PT, et al: Anatomically based guidelines for core needle biopsy of bone tumors:implications for limb-sparing surgery, Radiographics 27:189–206, 2007. Maharaj V, et al: Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver, Lancet 8:523– 535, 1986. Misra S, et al: Safety and diagnostic yield of transjugular renal biopsy, J Vasc Interv Radiol 19(4):546–551, 2008. Mok TS, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma, N Engl J Med 361(10):947–957, 2009. Moreira AL, et al: Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing, Clin Lung Cancer 13(5):334–339, 2012. Nasuti JF, et al: Diagnostic value and cost-effectiveness of on-site evaluation of fine-needle aspiration specimens: review of 5688 cases, Diagn Cytopathol 27:1–4, 2002. National Institutes of Health: NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”), NIH Consens State Sci Statements 19:1–25, 2002. Odisio BC, et al: CT-guided adrenal biopsy;comparison of ipsilateral decubitus versus prone positioning for biopsy approach, Eur Radiol 22(6):1233–1239, 2012. Ohlsson B, et al: Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours, Br J Surg 89:757–762, 2002. Patel P, et al: Improved accuracy of percutaneous biopsy using “cross and push” technique for patients with suspected malignant biliary stricutures, Cardiovasc Intervent Radiol 38(4):1005–1010, 2015. Perkins JD: Seeding risk following percutaneous approach to hepatocellular carcinoma, Liver Transpl 13(11):1603, 2007. Phillips MS, et al: Negative predictive value of imaging-guided abdominal biopsy results: cytologic classification and implications for patient management, AJR Am J Roentgenol 171:693–696, 1998. Piccinino F, et al: Complications following percutaneous liver biopsy: a multicentre retrospective study on 68,276 biopsies, J Hepatol 2:165–173, 1986. Ponchon T, et al: Methods, indications and results of percutaneous choledochoscopy: a series of 161 procedures, Ann Surg 223:26–36, 1996.

412.e2 PART 2  DIAGNOSTIC TECHNIQUES Rekhtman N, et al: Depletion of core needle biopsy cellularity and DNA content as a result of vigorous touch preparations, Arch Pathol Lab Med 139(7):907–912, 2015. Rockey DC, et al; American Association for the Study of Liver Disease: Liver biopsy, Hepatology 49(3):1017–1044, 2009. Ruben RA, Chopra S: Bile peritonitis after liver biopsy: nonsurgical management of a patient with an acute abdomen: a case report with review of the literature, Am J Gastroenterol 82:265–268, 1987. Ryan ER, et al: PET/CT-guided interventions: personnel radiation dose, Cardiovasc Intervent Radiol 36(4):1063–1067, 2013. Saborido BP, et al: Does preoperative fine needle aspiration-biopsy produce tumor recurrence in patients following liver transplantiation for hepatocellular carcinoma?, Transplant Proc 37:3874–3877, 2005. Sarti M, et al: Low-dose techniques in CT-guided interventions, Radiographics 32:1109–1119, 2012. Scagliotti GV, et al: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer, J Clin Oncol 26(21):3543–3551, 2008. Schiano TD, et al: Importance of specimen size in accurate needle liver biopsy evaluation of patients with chronic hepatitis C, Clin Gastroenterol Hepatol 3:930–935, 2005. Schotman SN, et al: Subcutaneous seeding of hepatocellular carcinoma after percutaneous needle biopsy, Gut 45:626–627, 1999. Sigel CS, et al: Subtyping of non-small cell lung carcinoma: a comparison of small biopsy and cytology specimens, J Thorac Oncol 6(11):1849–1856, 2011. Sofocleous CT, et al: CT-guided transvenous or transcaval needle biopsy of pancreatic and peripancreatic lesions, J Vasc Interv Radiol 15:1099–1104, 2004. Stattaus J, et al: MR-guided core biopsy with MR fluoroscopy using a short, wide-bore 1.5 Tesla scanner: feasibility and initial results, J Magn Reson Imaging 27(5):1181–1187, 2008. Stewart CJ, et al: Brush cytology in the assessment of pancreaticobiliary strictures: a review of 406 cases, J Clin Pathol 54:449–455, 2001.

Stewart CJ, et al: Comparison of fine needle aspiration cytology and needle core biopsy in the diagnosis of radiologically detected abdominal lesions, J Clin Pathol 55(2):93–97, 2002. Stigliano R, et al: Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach to HCC, Cancer Treat Rev 33(5):437–447, 2007. Swischuk JL, et al: Percutaneous transthoracic needle biopsy of the lung: review of 612 lesions, J Vasc Interv Radiol 9:347–352, 1998. Takeshita J, et al: CT-guided fine-needle aspiration and core needle biopsies of pulmonary lesions: a single-center experience with 750 biopsies in Japan, AJR Am J Roentgenol 204(1):29–34, 2015. Tran AA, et al: Tract embolization with gelatin sponge slurry for prevention of pneumothorax after percutaneous computed tomographyguided lung biopsy, Cardiovasc Intervent Radiol 37(6):1546–1553, 2014. Travis WD, et al: Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift, J Thorac Oncol 5(4):411–414, 2010. Tselikas L, et al: Percutaneous bone biopsies: comparison between flat-panel cone beam CT and CT-scan guidance, Cardiovasc Intervent Radiol 38:167–176, 2015. Tsou M-H, et al: CT-guided needle biopsy:Value of on-site cytopathologic evaluation of core specimen touch preparations, J Vasc Interv Radiol 20:71–76, 2009. Wang ZJ, et al: Immediate versus delayed treatment with EGFR tyrosine kinase inhibitors after first-line therapy in advanced non-smallcell lung cancer, Chin J Cancer Res 23(2):112–117, 2011. Weber A, et al: Diagnostic approaches for cholangiocarcinoma, World J Gastroenterol 14(26):4131–4136, 2008. Yang GC, et al: Distinguishing well-differentiated hepatocellular carcinoma from benign liver by the physical features of fine-needle aspirates, Mod Pathol 17:798–802, 2004. Yu SC, et al: US-guided percutaneous biopsy of small (<1 cm) hepatic lesions, Radiology 218:195–199, 2001.